Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

Abstract

Mitochondria are the central target of ischemic preconditioning and postconditioning cardioprotective strategies, which consist of either the application of brief intermittent ischemia/reperfusion (I/R) cycles or the administration of pharmacological agents. Such strategies reduce cardiac I/R injury by activating protective signaling pathways that prevent the exacerbated production of reactive oxygen/nitrogen species, inhibit opening of mitochondrial permeability transition pore and reduce apoptosis, maintaining normal mitochondrial function. Cardioprotection also involves the activation of mitochondrial quality control (MQC) processes, which replace defective mitochondria or eliminate mitochondrial debris, preserving the structure and function of the network of these organelles, and consequently ensuring homeostasis and survival of cardiomyocytes. Such processes include mitochondrial biogenesis, fission, fusion, mitophagy and mitochondrial-controlled cell death. This review updates recent advances in MQC mechanisms that are activated in the protection conferred by different cardiac conditioning interventions. Furthermore, the role of extracellular vesicles in mitochondrial protection and turnover of these organelles will be discussed. It is concluded that modulation of MQC mechanisms and recognition of mitochondrial targets could provide a potential and selective therapeutic approach for I/R-induced mitochondrial dysfunction.

A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury

“…Mitochondrial dysfunction is a key feature of IR injury [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ], and the pan-inhibition of δPKC, with δV1-1, prevents IR-induced increases in mitochondrial oxidant production, and decreases in ATP levels [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. However, the mechanism by which δPKC causes mitochondrial dysfunction, and the protein substrate that mediates it, have not been identified.…”

Aging of Vascular System Is a Complex Process: The Cornerstone Mechanisms

“…It has been shown that under I/R conditions, suppression of mitochondrial division is cardioprotective. Some recent studies also demonstrated that in order to maintain normal mitochondrial function and avoid the development of cardiac hypertrophy and heart failure, fused proteins OPA1, Mfn1 and Mfn2 are required [31].…”

Modulation of Inula racemosa Hook Extract on Cardioprotection by Ischemic Preconditioning in Hyperlipidaemic Rats

“…Next, Atr (20 M) reperfusion was conducted in the final episode of IPC. The heart isolated from HL rats was treated with a hydroalcoholic extract of IrA and then subjected to four cycles of preconditioning: 5 min of occlusion, followed by 5 min of reperfusion with the KH buffer after stabilization for 10 min (10). Next, IPC was conducted in the rat heart treated with IrA and Atr was administered intravenously.…”

“…Mitochondrial ATP-sensitive potassium channels (KATP) form when the PI3K/Akt pathway is activated and the mitochondrial permeability transition pore (MPTP) opening is blocked [ 6 - 8 ]. However, the cardioprotective effect of the IPC diminishes under some pathological conditions such as aging [ 9 ], high blood pressure [ 10 , 11 ], diabetes mellitus [ 12 , 13 ], and heart failure [ 14 , 15 ]. Hyperlipidemia (HL) is a major risk factor for IHD [ 16 ] and reduces the cardioprotective effects of the IPC.…”